The Neuropathology Sub-Core (NP) provides complete brain banking and neuropathology diagnostic services for the Pittsburgh ADRC with the goal of providing well-characterized tissues for research studies. Brain autopsies are performed on a 24 hour basis and the average post-mortem time over the past four years is ~6 hours. Over 150 frozen samples and CSF are banked. The brain is then fixed in 10% buffered formalin and 20 areas are taken for microscopic evaluation. Stains used include H&E, immunocytochemical (beta-A4 amyloid, tau, alpha-synuclein, and ubiquitin, TDP-43) and silver stains (Bielschowsky). Evaluation is performed using NIA-RI guidelines. Lewy Body pathology assessed per the DLB consensus criteria of McKeith et. al. Tissues and data are made available to investigators only after approval by the ADRC Executive Committee. During the last 5 years (2004-2008), the NP Sub-Core has evaluated a total of 289 cases: 115 of these were part of the ADRC cohort. Thirty-five of the 289 cases were part of ALS bank, 16 came from the Movement Disorders Clinic and 11 were from the Late Life Mood Disorder Cohort. 14 CJD cases (or rule out CJD) were also evaluated. 98 other cases were evaluated and included gross-only evaluations for brains that were removed for other ADCs or brain banking groups, medical autopsies for possible controls, and cases associated with the ADRC who were not part of the Cohort. Postmortem times for ADRC cohort cases with frozen material banked remained low at 5.1 hrs average. The NP Sub-Core provides regular updates to the NACC NP Database. The Sub-Core is also an active participant in local, national and international conferences. The Sub-Core maintains a reference laboratory (including a Ar/Kr laser confocal microscope) for development of quantitative analyses. The Genetics Sub-Core maintains a repository of DNA and genotypes on all participants of the Pittsburgh ADRC. The aims of the Genetics Sub-Core are: 1) to collect and bank DNA from blood and brain tissues from all participants in the Pittsburgh ADRC; 2), to generate genotype data for the APOE polymorphisms in the coding (codons 28, 112, 158) and regulatory (-491 A/T, -427 T/C, -219 G/T, -186 G/T and +113 G/C) regions, and other new genetic risk markers associated with late-onset Alzheimer's disease from DNA obtained in Aim 1; and 3) to provide banked DNA and genotype data to the ADRC Registry Database and to ADRC affiliated R01 grants, pilot projects and NIA repositories so that the DNA can be used for other genetic markers screening and genotype data can be used to assess the genetic risk for Alzheimer's disease.